The incidence of calcium phosphate (CaP) kidney stone disease has increased significantly over the last three decades. Patients suffering from CaP urolithiasis often experience stone recurrence despite pharmacological interventions, an indication to the suboptimal nature of the current medical regimen. The major metabolic risk factors predisposing to CaP stone formation are hypercalciuria, high urine pH, and hypocitraturia. Potassium citrate (KCit) is frequently prescribed to calcium stone formers because it increases urine citrate and lowers urine calcium. However, a concern is that, in CaP stone formers, these beneficial effects may be negated by a further rise in urine pH induced by KCit, and the net effect of KCit in CaP stone formers remains to be determined. An alternative strategy that is physiologically-based but not clinically-tested is citric acid (CitA) administratin that can potentially increase urine citrate without raising urine pH. Based on the knowledge and rationale stated above and our preliminary studies, we hypothesize that KCit and/or citric acid are potential countermeasures that attenuate the risk of recurrent stone formation in CaP stone formers. To test this hypothesis, we will examine in a short-term placebo-controlled cross-over metabolic study whether CitA or KCit can reduce CaP saturation (as brushite) in urine of CaP stone formers. Physicochemical assays will be applied in addition to computer-based stone risk prediction programs to assess risk of stone recurrence. This small scale clinical pilot study will use surrogate measures to test two simple regimens. It addresses a clinical question of utmost importance as we are in dire need of an effective therapy for patients with recurrent CaP stones, a group of stone formers that have not been specifically evaluated in past clinical trials. Results from this pilot study are likely to lead to full-scale randomized clinical trials with clinical outcomes for the prevention and treatment of recurrent CaP urolithiasis, an increasingly encountered condition in clinical practice. PUBLIC HEALTH RELEVANCE: Calcium phosphate kidney stones are increasingly encountered in clinical practice, and are highly recurrent and difficult to treat. This proposal wil test whether pharmacological therapy with potassium citrate or citric acid reduces the risk of recurrent stone formation in calcium phosphate stone formers. Results from this pilot study are likely to lead to full-scale randomized clinical trials for the prevention and treatment of recurret calcium phosphate kidney stones.